In the past year, a number of new findings were made possible by the availability of monoclonal antibodies to lymphocyte surface markers. Monoclonal antibody to HLA-DR antigen was used to study the source, distribution and functions of HLA-DR molecules on T and non-T lymphoid cells. The results indicate that DR is required for stimulation in autologous mixed lymphocyte reaction (MLR) and presentation of soluble antigen. Resting T cells do not synthesize or express detectable DR molecules but alloactivated T cells (purified with a pan-T monoclonal antibody) synthesize and express significant amounts of DR that is identical in charge and molecular weight to B cell DR from the responder. Most importantly, DR plus but not DR minus alloactivated T cells were suppressive of fresh MLRs and suppression was specific for the DR molecules of the stimulator cells; such antigen-specific suppressor T cells were inducible in all healthy individuals tested. In other studies, genetically restricted MLR suppressor T cells of a healthy donor were isolated from peripheral blood with a monoclonal antibody that recognized only 20% of the donor's T cells. All MLR suppression was mediated by these cells and these cells elaborated antigen-specific soluble suppressor factors. In another study, we showed that total lymphoid irradiation (TLI), a standard treatment for Hodgkin's disease and an experimental approach for the treatment of autoimmune disorders and prevention of allograft rejection, induced circulating MLR suppressor cells in patients who lack such cells prior to treatment. TLI-induced suppressor cells were nonspecific with respect to antigen and not genetically restricted with respect to responder. Thus, 3 types of MLR suppressor cells have been observed: 1) Genetically restricted cells of rare healthy individuals; 2) Antigen-specific, genetically unrestricted alloactivated cells; 3) Antigen nonspecific genetically unrestricted suppressor cells induced in vivo by TLI.